Synergistic effect of interleukin-1 beta and tumor necrosis factor alpha on PGE(2) production by articular chondrocytes does not involve PLA(2) stimulation
Synergistic effect of interleukin-1 beta and tumor necrosis factor alpha on PGE(2) production by articular chondrocytes does not involve PLA(2) stimulation
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DOI：
10.1006/excr.1996.0047
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发表时间：
1996-02-01
影响因子：
3.7
通讯作者：
Masliah, J
中科院分区：
文献类型：
--
作者：
Berenbaum, F;Jacques, C;Masliah, J
本研究探讨了兔关节软骨细胞（RAC）中两种促炎细胞因子肿瘤坏死因子（TNF）和白细胞介素-1 β (IL1)导致前列腺素E(2) （PGE(2)）产生增加的途径。原代培养兔关节软骨细胞分别与il - 1、TNF或两者孵育。测定花生四烯酸（AA）的释放、PGE(2)的产生以及胞质磷脂酶A(2) （cPLA(2)）、分泌磷脂酶A(2) （sPLA(2)）和环氧合酶（COX）的活性。利用特异性互补DNA探针，通过Northern blotting检测cPLA(2)、sPLA(2)和COX-2的mRNA水平。il - 1刺激的RAC与TNF的孵育进一步增加了PGE(2)的产生。这种协同作用不涉及PLA(2)刺激，因为AA释放、cPLA(2)和sPLA(2)活性或mRNA均未增加。相反，TNF增加了il - 1对COX-2活性和mRNA水平的影响，这些结果表明TNF和il - 1协同作用于关节软骨细胞中PGE(2)的产生。由于sPLA(2)和cPLA(2)似乎不参与，COX-2似乎是针对软骨降解的特定抗炎策略的最佳靶点。(C) 1996学术出版社，Inc.
This study investigates the ways in which two proinflammatory cytokines, tumor necrosis factor alpha (TNF) and interleulrin-1 beta (IL1), cause increased production of prostaglandin E(2) (PGE(2)) in rabbit articular chondrocytes (RAC). Rabbit articular chondrocytes in primary culture were incubated with IL1, TNF, or both. Arachidonic acid (AA) release, PGE(2) production, and the activities of cytosolic phospholipase A(2) (cPLA(2)), secreted phospholipase A(2) (sPLA(2)), and cyclooxygenase (COX) were measured. The mRNA levels of cPLA(2), sPLA(2), and COX-2 were also measured by Northern blotting, using specific complementary DNA probes. Incubation of IL1-stimulated RAC with TNF further increased PGE(2) production. This synergy did not involve PLA(2) stimulation, as there were no increases in AA release, cPLA(2) and sPLA(2) activities, or mRNA. In contrast, TNF increased the effect of IL1 on COX-2 activity and mRNA level, These results show that TNF and IL1 act in synergy in PGE(2) production in articular chondrocytes. As sPLA(2) and cPLA(2) do not seem to be involved, COX-2 appears to be the best target for a specific anti-inflammatory strategy against cartilage degradation. (C) 1996 Academic Press, Inc.